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BMP and FGF signaling interact to pattern mesoderm by controlling basic helix-loop-helix transcription factor activity.

TitleBMP and FGF signaling interact to pattern mesoderm by controlling basic helix-loop-helix transcription factor activity.
Publication TypeJournal Article
Year of Publication2018
AuthorsRow RH, Pegg A, Kinney BA, Farr GH, Maves L, Lowell S, Wilson V, Martin BL
JournalElife
Volume7
Date Published2018 Jun 07
ISSN2050-084X
Abstract

The mesodermal germ layer is patterned into mediolateral subtypes by signaling factors including BMP and FGF. How these pathways are integrated to induce specific mediolateral cell fates is not well understood. We used mesoderm derived from post-gastrulation neuromesodermal progenitors (NMPs), which undergo a binary mediolateral patterning decision, as a simplified model to understand how FGF acts together with BMP to impart mediolateral fate. Using zebrafish and mouse NMPs, we identify an evolutionarily conserved mechanism of BMP and FGF-mediated mediolateral mesodermal patterning that occurs through modulation of basic helix-loop-helix (bHLH) transcription factor activity. BMP imparts lateral fate through induction of Id helix loop helix (HLH) proteins, which antagonize bHLH transcription factors, induced by FGF signaling, that specify medial fate. We extend our analysis of zebrafish development to show that bHLH activity is responsible for the mediolateral patterning of the entire mesodermal germ layer.

DOI10.7554/eLife.31018
Alternate JournalElife
PubMed ID29877796
PubMed Central IDPMC6013256
Grant ListR03 AR065760 / AR / NIAMS NIH HHS / United States
Senior Fellowship in Basic Biomedical Science 103789/Z/14/Z / / Wellcome /
R03 AR065760 / / National Institute of Arthritis and Musculoskeletal and Skin Diseases /
Mr/K011200/1 / / Medical Research Council / United Kingdom
CAREER Award IOS1452928 / / National Science Foundation /
National Scientist Development Grant 13SDG14360032 / / American Heart Association /
/ / Wellcome Trust / United Kingdom
Publication institute
CRM